1.
Can GCSF-stimulated donor lymphocyte infusions improve outcomes for relapsed disease following allogeneic hematopoietic cell transplantation? A systematic review and meta-analysis
Kirkham, A. M., Bailey, A. J. M., Masurekar, A., Shorr, R., Bredeson, C., Sabloff, M., Allan, D. S.
Leukemia & lymphoma. 2022;:1-12
Abstract
Donor lymphocyte infusions (DLI) can produce graft-versus tumor effects to treat relapse after allogeneic hematopoietic cell transplantation, however, durable responses remain uncommon. A systematic review and meta-analysis are needed to clarify whether DLI collected after stimulation with granulocyte colony-stimulating factor (GCSF; G-DLI) can improve clinical outcomes. Sixteen studies (4 controlled) involving 585 patients were identified in a systematic search up to 17 September 2020. A meta-analysis demonstrated no significant difference in the risk of all-cause mortality (RR: 0.94, 95% CI 0.52-1.68, p = 0.82; n = 3 studies) or relapse-related mortality (RR: 0.72, 0.44-1.18, p = 0.19; n = 3 studies) between G-DLI and conventional DLI (C-DLI) groups. G-DLI products had similar mean CD3+ cells compared to C-DLI products, but median CD34+ cells/kg were increased. No improvement in disease progression, complete response rates, or risk of developing GVHD was observed with G-DLI, however, greater non-relapse mortality was observed compared to C-DLI. Alternative approaches to enhancing graft-versus-tumor effects are needed.
2.
Impact of natural killer cells on outcomes after allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis
Mushtaq, M. U., Shahzad, M., Shah, A. Y., Chaudhary, S. G., Zafar, M. U., Anwar, I., Neupane, K., Khalid, A., Ahmed, N., Bansal, R., et al
Frontiers in Immunology. 2022;13:1005031
Abstract
BACKGROUND Natural killer (NK) cells play a vital role in early immune reconstitution following allogeneic hematopoietic stem cell transplantation (HSCT). METHODS A literature search was performed on PubMed, Cochrane, and Clinical trials.gov through April 20, 2022. We included 21 studies reporting data on the impact of NK cells on outcomes after HSCT. Data was extracted following the PRISMA guidelines. Pooled analysis was done using the meta-package (Schwarzer et al.). Proportions with 95% confidence intervals (CI) were computed. RESULTS We included 1785 patients from 21 studies investigating the impact of NK cell reconstitution post-HSCT (8 studies/1455 patients), stem cell graft NK cell content (4 studies/185 patients), therapeutic NK cell infusions post-HSCT (5 studies/74 patients), and pre-emptive/prophylactic NK cell infusions post-HSCT (4 studies/77 patients). Higher NK cell reconstitution was associated with a better 2-year overall survival (OS) (high: 77%, 95%CI 0.73-0.82 vs low: 55%, 95%CI 0.37-0.72; n=899), however, pooled analysis for relapse rate (RR) or graft versus host disease (GVHD) could not be performed due to insufficient data. Higher graft NK cell content demonstrated a trend towards a better pooled OS (high: 65.2%, 95%CI 0.47-0.81 vs low: 46.5%, 95%CI 0.24-0.70; n=157), lower RR (high: 16.9%, 95%CI 0.10-0.25 vs low: 33%, 95%CI 0.04-0.72; n=157), and lower acute GVHD incidence (high: 27.6%, 95%CI 0.20-0.36 vs low: 49.7%, 95%CI 0.26-0.74; n=157). Therapeutic NK or cytokine-induced killer (CIK) cell infusions for hematologic relapse post-HSCT reported an overall response rate (ORR) and complete response (CR) of 48.9% and 11% with CIK cell infusions and 82.8% and 44.8% with NK cell infusions, respectively. RR, acute GVHD, and chronic GVHD were observed in 55.6% and 51.7%, 34.5% and 20%, and 20.7% and 11.1% of patients with CIK and NK cell infusions, respectively. Pre-emptive donor-derived NK cell infusions to prevent relapse post-HSCT had promising outcomes with 1-year OS of 69%, CR rate of 42%, ORR of 77%, RR of 28%, and acute and chronic GVHD rates of 24.9% and 3.7%, respectively. CONCLUSION NK cells have a favorable impact on outcomes after HSCT. The optimal use of NK cell infusions post-HSCT may be in a pre-emptive fashion to prevent disease relapse.
3.
Prophylactic donor lymphocyte infusion for relapse prevention: a meta-analysis
Poonsombudlert, K., Kewcharoen, J., Prueksapraopong, C., Limpruttidham, N.
Japanese journal of clinical oncology. 2020
Abstract
OBJECTIVE Primary disease relapse (PDR) of malignant hematologic conditions after standard hematopoietic stem cell transplant (HSCT) is one of the most challenging diseases; therefore ongoing researches are aiming at relapse prevention and minimizing the transplant-related side effects. Prophylactic donor lymphocytes (pDLI) had been proposed as a valuable strategy for PDR prevention, but early studies had been discouraging due to the limited benefit and possible association with acute graft-versus-host disease (aGVHD). Therefore, we conducted a meta-analysis to evaluate the association between pDLI use, PDR, aGVHD and OS. METHOD We performed a comprehensive literature search in MEDLINE, Cochrane library and Embase database from inception to May 2019 for studies that evaluated the association between pDLI and PDR. We conducted a random effect meta-analysis of 9 studies involving a total of 748 participants (pDLI = 398, non-pDLI = 350) and reported the pooled odd ratio (OR) for association of pDLI use, PDR, aGVHD and OS. RESULT We found a significant decreased odd of PDR in the pDLI group (pooled OR = 0.42, 95% CI 0.30-0.58, I2 = 0%), but there was no significant increased odd of aGVHD (pooled OR of 0.98, 95% CI 0.56-1.72, I2 = 0.8%). We also found that there was an increased odd of overall survival (OS) (pooled OR 3.17, 95% CI 1.85-5.45, I2 = 50.2%). CONCLUSION There are significantly decreased odd of PDR and increased odd of OS in the pDLI group compared to the control group, but there is no statistically significant increased odd of aGVHD as suggested by previous studies. We concluded that pDLI is a potentially valuable method for post-transplant PDR prevention.